The studies will examine the development and survival of peripheral glial cells (Schwann cells) in the chicken embryo. The major objectives of the planned studies are to characterize the cellular and molecular development of Schwann cells before, during and after the normal period of programmed cell death of these cells. A central focus of the research is to identify and characterize the role of axon-derived signals in the differentiation and maintenance (survival) of glial cells. In the first Aim, in vivo studies will examine the effects of modifying putative axon-derived signals and will characterize the anatomical relationship of axon-Schwann cell interactions at the ultrastructural level. In the second Aim, purified culture of Schwann cells will be examined for their response (survival, proliferation, differentiation) to putative glial growth factors. In the third Aim, in vivo studies will examine the growth factors and conditions identified in Aim 2, that promote the survival and differentiation of Schwann cells in vitro, for their physiological relevance in vivo. Together, the studies will advance our understanding of the normal development of glia and may reveal aspects of glial development and survival that are perturbed in peripheral neuropathies and during nerve regeneration following injury.